Abstract
Background: The underlying genetic abnormalities of rare familial idiopathic epilepsy have been
identified, such as mutation in KCNQ2, a K+ channel gene. Yet, few genetic abnormalities have been reported for commoner epilepsy,
i.e., sporadic idiopathic epilepsy, which share a phenotype similar to those of familial
epilepsy. Objective: To search for the genetic cause of seizures in a girl with the diagnosis of non-familial
benign neonatal convulsions, and define the consequence of the genetic abnormality
identified. Methods: Genetic abnormality was explored within candidate genes for benign familial neonatal
and infantile convulsions, such as KCNQ2, 3, 5, KCNE2, SCN1A and SCN2A. The electrophysiological properties of the channels harboring the identified mutation
were examined. Western blotting and immunostaining were employed to characterize the
expression and intracellular localization of the mutant channel molecules. Results: A novel heterozygous mutation (c.910-2delTTC or TTT, Phe304del) of KCNQ2 was identified in the patient. The mutation was de novo verified by parentage analysis. The mutation was associated with impaired functions
of KCNQ K+ channel. The mutant channels were expressed on the cell surface. Conclusion: The mutant Phe304del of KCNQ2 leads to null function of the KCNQ K+ channel but the mutation does not alter proper channel sorting onto the cell membrane.
Our findings indicate that the genes responsible for rare inherited forms of idiopathic
epilepsy could be also involved in sporadic forms of idiopathic epilepsy and expand
our notion of the involvement of molecular mechanisms in the more common forms of
idiopathic epilepsy.
Keywords
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References
- Are some idiopathic epilepsies disorders of ion channels? A working hypothesis.Epilepsy Res. 2000; 41: 191-204
- Genetics abnormalities underlying familial epilepsy syndromes.Brain Dev. 2002; 24: 211-222
- A novel splicing mutation in KCNQ2 in a multigenerational family with BFNC followed for 25 years.Epilepsia. 2006; 47: 851-859
- A novel mutation in KCNQ2 gene causes benign familial neonatal convulsions in a Chinese family.J. Neurol. Sci. 2004; 221: 31-34
- De novo KCNQ2 mutations in patients with benign neonatal seizures.Neurology. 2004; 63: 2155-2158
- A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation.Neurology. 2004; 63: 57-65
- KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum.Brain. 2003; 126: 2726-2737
- A novel mutation of KCNQ3 (c.925T>C) in a Japanese family with benign familial neonatal convulsions (BFNC2).Ann. Neurol. 2000; 47: 822-826
- A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.Nat. Genet. 1998; 18: 25-29
- A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family.Nat. Genet. 1998; 18: 53-55
- A potassium channel mutation in neonatal human epilepsy.Science. 1998; 279: 403-406
- Mutations of neuronal voltage-gated Na+ channel α1 subunit gene SCN1A in core severe myoclonic epilepsy in infancy (SMEI) and in borderline SMEI (SMEB).Epilepsia. 2004; 45: 140-148
- A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy.Neurology. 1999; 53: 1749-1753
- Linkage and association analyses of the osteoprotegerin gene locus with human osteoporosis.J. Hum. Genet. 2002; 47: 400-406
- Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.Pflügers Arch. 1981; 391: 85-100
- Immunoblotting analysis of plasma protein processing in the secretory pathway of rat liver: identification of proteolytic conversion sites of complement pro-C3 and prohaptoglobin.J. Biochem. (Tokyo). 1986; 100: 1669-1675
- M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 subunit.FEBS Lett. 2000; 480: 137-141
- Sodium-channel defects in benign familial neonatal-infantile seizures.Lancet. 2002; 360: 851-852
- The LGI1 gene involved in lateral temporal lobe epilepsy belongs to a new subfamily of leucine-rich repeat proteins.FEBS Lett. 2002; 519: 71-76
- Involvement of KCNQ2 subunits in [3H]dopamine release triggered by depolarization and pre-synaptic muscarinic receptor activation from rat striatal synaptosomes.J. Neurochem. 2007; 102: 179-193
- Calmodulin is an auxiliary subunit of KCNQ2/3 potassium channels.J. Neurosci. 2002; 22: 7991-8001
- Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy.J. Biol. Chem. 2000; 275: 13343-13348
- Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy.Proc. Natl. Acad. Sci. USA. 2000; 97: 4914-4919
- KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel.Science. 1998; 282: 1890-1893
- Disruption of the epilepsy KCNQ2 gene results in neural hyperexcitability.J. Neurochem. 2000; 75: 28-33
- A novel KCNQ2 K+ channel mutation in benign neonatal convulsions and centrotemporal spikes.Neurology. 2003; 61: 131-134
- A de novo mutation in sporadic nocturnal frontal lobe epilepsy.Ann. Neurol. 2000; 48: 264-267
Article info
Publication history
Published online: September 01, 2008
Accepted:
May 23,
2008
Received in revised form:
May 12,
2008
Received:
January 7,
2008
Identification
Copyright
© 2008 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
